Epilepsy is defined as the repeated occurrence of unprovoked seizures. One of the most common neurological disorders, epilepsy affects approximately 2.5 million Americans of all ages and backgrounds, and more than 60 million people worldwide. Based on modest estimates, at least one third of individuals diagnosed with epilepsy suffer from pharmacoresistance and intolerable side effects. Additionally, current antiepileptic drugs do little to prevent development of epilepsy (i.e., epileptogenesis) or to modify the progression of epilepsy. Therefore, therapeutic alternatives are urgently needed.
In contrast to systemic drug delivery, focal drug delivery to the brain is generally devoid of systemic side effects and holds promise for the therapy of epilepsy, which is frequently of focal origin. The recent identification of focal adenosine deficiency as major cause for seizure generation provides a neurochemical rationale for focal adenosine augmentation therapies (AATs). Focal AATs can be accomplished by implanting adenosine releasing devices or cells into the vicinity of an epileptogenic focus. AATs are devoid of systemic and sedative side effects, and augmentation of the adenosine response can suppress experimental seizures otherwise refractory to standard antiepileptic drugs. Thus, AATs hold promise for the therapy of refractory focal epilepsies. The experimental AATs are not suitable for clinical development, however, due to the use of animal cells or the short-term duration of therapeutic effect in some of the approaches. Further clinical development of AATs calls for the slow and sustained release of adenosine from safe and biocompatible brain implants.